Influence of the interaction between Ac-SDKP and Ang II signal on the development and progression of silicotic fibrosis / 解放军医学杂志

ABSTRACT

Objective To investigate the changes of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) and angiotensin converting enzyme (ACE)/angiotensin II(Ang II)/angiotensin II type 1 receptor (AT1R) axis and their impact on the development and progression of silicotic fibrosis. MethodsSixty male Wistar rats were randomly divided into 6 groups (n=10). The rats inhaled dust for 0, 2, 4, 8, 12, and 16 weeks (w) respectively to reproduce silicosis model. HE staining was performed to observe the pathological changes of the lung tissue. The expression of α smooth muscle actin (α-SMA), collagen I (Col I), fibronectin (Fn), ACE and AT1R were measured by Western blotting. The levels of Ac-SDKP and Ang II in lung tissue were detected by ELISA. ResultsMacrophage infiltration and widened alveolar wall were observed by HE staining in the silicosis 2-w group. Isolated cell lesions which composed of macrophages were seen in silicosis 4-w group. The alveolar wall widened obviously and the number of silicotic nodules increased at 8w and 12w. The fusion of silicotic lesions, interstitial fibrosis and fibrous lesions were observed at 16w. Compared with control group, the expressions of α-SMA, Col I and Fn protein in silicosis 4-, 8-, 12-, and 16-w group increased gradually. In silicosis 2-, 4-, 8-, 12-, 16-w group, the expressions of ACE, Ang II and AT1R gradually increased compared to the control. The level of Ac-SDKP in the lung tissue of silicosis 2-w group was significantly higher than that in control group, and then decreased gradually, and significantly lower in the silicosis 12- and 16-w group than the control (P<0.05). ConclusionAlong with the development and progression of silicosis, ACE, Ang II, and AT1R expressions gradually increase in local lung tissue, while the expression of Ac-SDKP gradually decreases. Ac-SDKP and Ang II signal would participate the silicotic fibrosis process in rats.